9308 RESULTS
COMMENT This interesting work adds to a growing number of reports that tau can co-aggregate with RNA and RNA-binding proteins. Lester and colleagues further show that this leads to disruptions in nuclear compartments, such as speckles, that have critical roles in ...
COMMENT This lovely study from the Parker lab further implicates tau as a splicing disruptor and identifies RNAs that are sequestered within tau aggregates (Raj et al., 2018; Apicco et al., 2019; Hsieh et al., 2019). While the mechanistic aspect of the paper ...
COMMENT The presence of tau has been noted in the nucleus for years, although the focus on cytoplasmic tau has biased the field away from the idea that tau might have a nuclear function (Maina et al., 2018; Mansuroglu et al., 2016). Under basal conditions, non ...
COMMENT Many thanks for putting together such a comprehensive review of GENUS work reported at ADPD. I’d like to add that three additional groups have independently replicated our preclinical data on GENUS. Park et. al. sought to determine whether treadmill ...
COMMENT Why doesn't Biogen take the learning from the first two trials and carefully design a trial that can support their contention of efficacy? If they are as certain as their press releases indicate (some of them targeting patients and their families), ...
COMMENT This is an exciting set of data from the Holtzman group that adds another piece to the puzzle of APOE’s role as a risk factor for Alzheimer’s Disease (AD). In this paper, Wang et al. use the P301S mouse model of AD, expressing either ApoE3 or ApoE4, and ...
COMMENT Two comments: 1) This study, however impressive, has a limitation: There is no Aβ pathology. Aβ uptake by astrocytes damages their endolysosomal system (Sanchez-Mico et al., 2021). Thus, the question is: How would astrocytes damaged by Aβ respond to Tau ...
COMMENT The new study in Neuron by Wang and colleagues, led by David Holtzman, Washington University, St. Louis, strengthens the evidence that APOE4 acts not only by gain of toxic function, but that APOE4 promotes multiple features of the classical Alzheimer’s ...
COMMENT I believe this to be a very important paper. A CD33 antibody that mimics the D2 phenotype, rather than just functionally eliminating CD33, could be of great value in treating Alzheimer's disease. Promoting healthy non-inflammatory microglia ...
COMMENT This new study fits with previous work from the Holtzman lab showing that ApoE4 knock-in exacerbates the neuroinflammation and neurodegeneration that occurs in this tauopathy model, while ApoE4 reduction by antisense oligonucleotide treatment opposes ...
COMMENT This paper by Wang et al. describes multiple effects of inducibly removing astrocytic APOE isoforms (APOE3 or APOE4) in a tau P301S mouse model. This model system is powerful in that it allows the researchers to isolate the contribution of astrocytic APOE ...
COMMENT This is a really important and definitive study demonstrating that astrocyte-derived ApoE has a major impact on tau accumulation and associated pathologies. Even though many labs are studying microglial ApoE in Alzheimer’s disease, the major source of ...
COMMENT Stefan Lichtenthaler gave an outstanding talk at AD/PD 2021. He presented very compelling mass spectrometry data that GP130 is a robust BACE1 substrate. It will be interesting to see what role this new BACE1 substrate may have regarding the cognitive ...
COMMENT I found it very interesting that Eisai did not observe the cognitive worsening that other BACE1 inhibitors have reported. Given that the majority of the other BACE1 inhibitors exhibited the cognitive worsening side effect, I originally concluded the ...
COMMENT The finding that elenbecestat largely avoided the cognitive worsening seen in studies with other BACE inhibitors is very encouraging. I take this as clear evidence that BACE1 inhibition can be achieved in a safe manner. In hindsight it appears that the ...
